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Journal of Clinical Medicine Nov 2023Tinnitus assessment and outcome measurement are complex, as tinnitus is a purely subjective phenomenon. Instruments used for the outcome measurement of tinnitus in the... (Review)
Review
OBJECTIVE
Tinnitus assessment and outcome measurement are complex, as tinnitus is a purely subjective phenomenon. Instruments used for the outcome measurement of tinnitus in the context of clinical trials include self-report questionnaires, visual analogue or numeric rating scales and psychoacoustic measurements of tinnitus loudness. For the evaluation of therapeutic interventions, it is critical to know which changes in outcome measurement instruments can be considered as clinically relevant. For this purpose, the concept of the minimal clinically important difference (MCID) has been introduced.
STUDY DESIGN
Here we performed a literature research in PubMed in order to identify for which tinnitus outcome measurements MCID criteria have been estimated and which of these estimates fulfil the current methodological standards and can thus be considered as established.
RESULTS
For most, but not all tinnitus outcome instruments, MCID calculations have been performed. The MCIDs for the Tinnitus Handicap Inventory (THI), the Tinnitus Questionnaire (TQ), the Tinnitus Functional Index (TFI) and visual analogue scales (VAS) vary considerably across studies. Psychoacoustic assessments of tinnitus such as loudness matching have not shown sufficient reliability and validity for the use as an outcome measurement.
CONCLUSION
Future research should aim at the confirmation of the available estimates in large samples involving various therapeutic interventions and under the consideration of time intervals and baseline values. As a rule of thumb, an improvement of about 15% can be considered clinically meaningful, analogous to what has been seen in other entirely subjective pathologies like chronic pain.
PubMed: 38002730
DOI: 10.3390/jcm12227117 -
Gesundheitswesen (Bundesverband Der... Sep 2023Schizophrenia psychoses can be treated much better today due to the introduction of antipsychotics about 70 years ago in conjunction with the implementation of specific... (Review)
Review
Schizophrenia psychoses can be treated much better today due to the introduction of antipsychotics about 70 years ago in conjunction with the implementation of specific psychotherapies. However, current treatment options are still limited in the area of negative symptoms and disease-associated cognitive deficits. In the last 15 years, randomised controlled trials (RCTs) have been able to show that physical training and especially endurance training could represent a comprehensive complementary treatment approach and could lead to a significant improvement in positive, but especially also in negative symptoms and cognitive deficits. As a result, sports therapy for schizophrenia psychoses has found its way not only into the national treatment guidelines of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Neurology (DGPPN), but also into European recommendations such as those of the European Psychiatric Association (EPA). With the introduction of the "Living guideline" format (here an update takes place at least once a year), a broader implementation in health care will be easier in the future. Based on a narrative review, this paper describes the process of implementing sports therapy for schizophrenia psychoses from its beginnings to its incorporation into guidelines and can be applied analogously to other forms of therapy.
Topics: Humans; Germany; Schizophrenia; Psychotherapy; Psychiatry; Psychotic Disorders
PubMed: 37751760
DOI: 10.1055/a-2129-7421 -
Inorganic Chemistry May 2024A family of rare-earth complexes [RE(III) = Y, La, Gd, Tb, Dy, and Er] with doubly reduced dibenzo[,]cyclooctatetraene (DBCOT) has been synthesized and structurally...
A family of rare-earth complexes [RE(III) = Y, La, Gd, Tb, Dy, and Er] with doubly reduced dibenzo[,]cyclooctatetraene (DBCOT) has been synthesized and structurally characterized. X-ray diffraction analysis confirms that all products of the [RE(DBCOT)(THF)][RE(DBCOT)] composition consist of the anionic sandwich [RE(DBCOT)] and the cationic counterpart [RE(DBCOT)(THF)]. Within the sandwich, two elongated π decks are slightly bent toward the metal center (avg. 7.3°) with a rotation angle of 35.9-37.6°. The RE(III) ion is entrapped between the central eight-membered rings of DBCOT in a η fashion. The trends in the RE-COT bond lengths are consistent with the variations of the ionic radii of RE(III) centers. The H NMR spectra of the diamagnetic Y(III) and La(III) analogues illustrate the distinct solution behavior for the cationic and anionic parts in this series. Magnetic measurements for the Dy analogue reveal single-molecule magnetism, which was rationalized by considering the effect of crystal-field splitting for both building units analyzed by electronic structure calculations.
PubMed: 38374612
DOI: 10.1021/acs.inorgchem.3c04249 -
Journal of Medicinal Chemistry Aug 2023Here, we designed three d-GLP-2 agonists that activated the glucagon-like peptide-2 receptor (GLP-2R) cyclic adenosine monophosphate (cAMP) accumulation without...
Here, we designed three d-GLP-2 agonists that activated the glucagon-like peptide-2 receptor (GLP-2R) cyclic adenosine monophosphate (cAMP) accumulation without stimulating the glucagon-like peptide-1 receptor (GLP-1R). All the d-GLP-2 agonists increased the protein kinase B phosphorylated (p-AKT) expression levels in a time- and concentration-dependent manner in vitro. The most effective d-GLP-2 analogue boosted the AKT phosphorylation 2.28 times more effectively compared to the native l-GLP-2. The enhancement in the p-AKT levels induced by the d-GLP-2 analogues could be explained by GLP-2R's more prolonged activation, given that the d-GLP-2 analogues induce a lower β-arrestin recruitment. The higher stability to protease degradation of our d-GLP-2 agonists helps us envision their potential applications in enhancing intestinal absorption and treating inflammatory bowel illness while lowering the high dosage required by the current treatments.
Topics: Proto-Oncogene Proteins c-akt; Glucagon-Like Peptide-2 Receptor; Peptides; Phosphorylation; Cyclic AMP; Glucagon-Like Peptide 2; Glucagon-Like Peptide-1 Receptor
PubMed: 37491005
DOI: 10.1021/acs.jmedchem.3c00464 -
Advances in Therapy Sep 2023This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1%... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized Multicenter Clinical Trial Comparing 0.1% Brimonidine/0.5% Timolol Versus 1% Dorzolamide/0.5% Timolol as Adjuncts to Prostaglandin Analogues: Aibeta Crossover Study.
INTRODUCTION
This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues.
METHODS
A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews.
RESULTS
BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation.
CONCLUSION
As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.
TRIAL REGISTRATION NUMBER
jRCTs051190125.
Topics: Humans; Timolol; Glaucoma, Open-Angle; Cross-Over Studies; Antihypertensive Agents; Ophthalmic Solutions; Brimonidine Tartrate; Intraocular Pressure; Prostaglandins, Synthetic; Drug Combinations
PubMed: 37452961
DOI: 10.1007/s12325-023-02589-9 -
Antiviral Research Jul 2023Genital herpes, most frequently caused by herpes simplex virus 2 (HSV-2) infection, is one of the most prevalent sexually transmitted infections. The current rationale...
Genital herpes, most frequently caused by herpes simplex virus 2 (HSV-2) infection, is one of the most prevalent sexually transmitted infections. The current rationale for the treatment of HSV-2 infection involves nucleoside analogs (e.g. acyclovir) to suppress reactivation. Enzymatic oxysterols are endogenous 27-carbon atoms molecules produced by enzymatic cholesterol oxidation, and recently emerged as a broad-spectrum host targeting antivirals. In this study, we screened selected members of an in-house synthesized library of oxysterol analogs for their activity against HSV-2, identifying three compounds, named PFM064, PFM067, and PFM069, endowed with 50% effective concentrations (EC) in the micromolar range, without exerting any apparent cytotoxicity. Moreover, the results obtained showed the ability of the novel derivatives to inhibit both cell-to-cell fusion induced by HSV-2, and the production of an intracellular viral progeny. Further experiments performed with PFM067 (which was selected for more-in-depth studies as the most effective synthetic analog) showed that these molecules act in a late stage of HSV-2 replicative cycle, by sequestering viral glycoproteins in the Golgi compartment, and likely inhibiting the nuclear egress of neo-synthetized viral capsids. Taken together, these results point to PFM067 as a promising chemical scaffold for the development of novel herpetic antivirals.
Topics: Humans; Herpesvirus 2, Human; Virus Replication; Oxysterols; Herpes Simplex; Antiviral Agents
PubMed: 37164189
DOI: 10.1016/j.antiviral.2023.105634 -
Journal of Peptide Science : An... Feb 2024Insulin replacement therapy is essential for the management of diabetes. However, despite the relative success of this therapeutic strategy, there is still a need to...
Insulin replacement therapy is essential for the management of diabetes. However, despite the relative success of this therapeutic strategy, there is still a need to improve glycaemic control and the overall quality of life of patients. This need has driven research into orally available, glucose-responsive and rapid-acting insulins. A key consideration during analogue development is formulation stability, which can be improved via the replacement of insulin's A6-A11 disulfide bond with stable mimetics. Unfortunately, analogues such as these require extensive chemical synthesis to incorporate the nonnative cross-links, which is not a scalable synthetic approach. To address this issue, we demonstrate proof of principle for the semisynthesis of insulin analogues bearing nonnative A6-A11 cystine isosteres. The key feature of our synthetic strategy involves the use of several biosynthetically derived peptide precursors which can be produced at scale cost-effectively and a small, chemically synthesised A6-A11 macrocyclic lactam fragment. Although the assembled A6-A11 lactam insulin possesses poor biological activity in vitro, our synthetic strategy can be applied to other disulfide mimetics that have been shown to improve thermal stability without significantly affecting activity and structure. Moreover, we envisage that this new semisynthetic approach will underpin a new generation of hyperstable proteomimetics.
Topics: Humans; Insulin; Lactams; Quality of Life; Cystine; Disulfides
PubMed: 37697741
DOI: 10.1002/psc.3542 -
Scientific Reports Dec 2023Secondary minerals in lava tubes on Earth provide valuable insight into subsurface processes and the preservation of biosignatures on Mars. Inside lava tubes near the...
Secondary minerals in lava tubes on Earth provide valuable insight into subsurface processes and the preservation of biosignatures on Mars. Inside lava tubes near the Hawaii-Space Exploration and Analog Simulation (HI-SEAS) habitat on the northeast flank of Mauna Loa, Hawaii, a variety of secondary deposits with distinct morphologies were observed consisting of mainly sodium sulphate powders, gypsum crystalline crusts, and small coralloid speleothems that comprise opal and calcite layers. These secondary deposits formed as a result of hydrological processes shortly after the formation and cooling of the lava tubes and are preserved over long periods of time in relatively dry conditions. The coralloid speleothem layers are likely related to wet and dry periods in which opal and calcite precipitates in cycles. Potential biosignatures seem to have been preserved in the form of porous stromatolite-like layers within the coralloid speleothems. Similar secondary deposits and lava tubes have been observed abundantly on the Martian surface suggesting similar formation mechanisms compared to this study. The origin of secondary minerals from tholeiitic basalts together with potential evidence for microbial processes make the lava tubes near HI-SEAS a relevant analog for Martian surface and subsurface environments.
PubMed: 38114584
DOI: 10.1038/s41598-023-48923-7 -
The Interactions of Soy Protein and Wheat Gluten for the Development of Meat-like Fibrous Structure.Molecules (Basel, Switzerland) Nov 2023Consumers who are environmentally and health conscious are increasingly looking for plant-based alternatives to replace animal-based products in their daily diets. Among... (Review)
Review
Consumers who are environmentally and health conscious are increasingly looking for plant-based alternatives to replace animal-based products in their daily diets. Among these alternatives, there is a growing demand for meat analogues that closely resemble the taste and texture of meat. As a result, significant efforts have been dedicated to developing meat analogues with a desirable meat-like structure. Currently, soy protein and wheat gluten are the main ingredients used for producing these meat analogues due to their availability and unique functionalities. This study observed that high moisture extrusion at moisture levels of 50-80% has become a common approach for creating fibrous structures, with soy protein and wheat gluten being considered incompatible proteins. After the structuring process, they form two-phase filled gels, with wheat gluten acting as the continuous phase and soy protein serving as a filler material. Moreover, the formation of soy protein and wheat gluten networks relies on a combination of covalent and non-covalent interaction bonds, including hydrogen bonds that stabilize the protein networks, hydrophobic interactions governing protein chain associations during thermo-mechanical processes, and disulfide bonds that potentially contribute to fibrous structure formation. This review provides case studies and examples that demonstrate how specific processing conditions can improve the overall structure, aiming to serve as a valuable reference for further research and the advancement of fibrous structures.
Topics: Animals; Soybean Proteins; Triticum; Glutens; Meat; Hydrogen Bonding
PubMed: 37959850
DOI: 10.3390/molecules28217431 -
Nature Communications Mar 2024Extensive investigations on the moiré magic angle in twisted bilayer graphene have unlocked the emerging field-twistronics. Recently, its optics analogue, namely...
Extensive investigations on the moiré magic angle in twisted bilayer graphene have unlocked the emerging field-twistronics. Recently, its optics analogue, namely opto-twistronics, further expands the potential universal applicability of twistronics. However, since heat diffusion neither possesses the dispersion like photons nor carries the band structure as electrons, the real magic angle in electrons or photons is ill-defined for heat diffusion, making it elusive to understand or design any thermal analogue of magic angle. Here, we introduce and experimentally validate the twisted thermotics in a twisted diffusion system by judiciously tailoring thermal coupling, in which twisting an analog thermal magic angle would result in the function switching from cloaking to concentration. Our work provides insights for the tunable heat diffusion control, and opens up an unexpected branch for twistronics -- twisted thermotics, paving the way towards field manipulation in twisted configurations including but not limited to fluids.
PubMed: 38461277
DOI: 10.1038/s41467-024-46247-2